MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma.
OBJECTIVE
To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma.


METHODS
A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence.


RESULTS
A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma.


CONCLUSIONS
MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.
Sadones
J
J
Medical Oncology, UZ Brussel, Brussels, Belgium.
Michotte
A
A
Veld
P
P
Chaskis
C
C
Sciot
R
R
Menten
J
J
Joossens
E J R
EJ
Strauven
T
T
D'Hondt
L A
LA
Sartenaer
D
D
Califice
S F E H
SF
Bierau
K
K
Svensson
C
C
De Grève
J
J
Neyns
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000401:mortality; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide